SHC1

SHC-transforming protein 1 ;
SHC-transforming protein 3 ;
SHC-transforming protein A ;
Src homology 2 domain-containing-transforming protein C1 ;
SH2 domain protein C1 ;

domain:In response to a variety of growth factors , isoform p46Shc and isoform p52Shc bind to phosphorylated Trk receptors through their phosphotyrosine binding (PID) and/or SH2 domains. The PID and SH2 domains bind to specific phosphorylated tyrosine residues in the Asn-Pro-Xaa-Tyr (P) motif of the Trk receptors. Isoform p46Shc and isoform p52Shc are in turn phosphorylated on three tyrosine residues within the extended proline-rich domain. These phosphotyrosines act as docking site for GRB2 and thereby are involved in Ras activation. ,function:Signaling adapter that couples activated growth factor receptors to signaling pathway. Isoform p46Shc and isoform p52Shc , once phosphorylated , couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation , but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants , cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span. ,PTM:Phosphorylated by activated epidermal growth factor receptor. Isoform p46Shc and isoform p52Shc are phosphorylated on tyrosine residues of the Pro-rich domain. Isoform p66Shc is phosphorylated on Ser-36 upon treatment with insulin , hydrogen peroxide or irradiation with ultraviolet light. ,similarity:Contains 1 PID domain. ,similarity:Contains 1 SH2 domain. ,subcellular location:Localized to the mitochondria matrix. Targeting of isoform p46Shc to mitochondria is mediated by its first 32 amino acids , which behave as a bona fide mitochondrial targeting sequence. Isoform p52Shc and isoform p66Shc , that contain the same sequence but more internally located , display a different subcellular localization. ,subunit:Interacts with the Trk receptors in a phosphotyrosine-dependent manner. Interacts with the NPXY motif of tyrosine-phosphorylated IGF1R and INSR in vitro via the PID domain. Once activated , binds to GRB2. Interacts with tyrosine-phosphorylated CD3T. Interacts with the N-terminal region of APS. Interacts with phosphorylated LRP1 and IRS4. Interacts with INPP5D/SHIP1 and INPPL1/SHIP2. ,tissue specificity:Widely expressed. Expressed in neural stem cells but absent in mature neurons. ,

MAPKKK cascade , activation of MAPK activity , regulation of DNA replication , protein amino acid phosphorylation ,phosphorus metabolic process , phosphate metabolic process , cell surface receptor linked signal transduction , enzyme linked receptor protein signaling pathway , transmembrane receptor protein tyrosine kinase signaling pathway ,epidermal growth factor receptor signaling pathway , regulation of epidermal growth factor receptor activity ,intracellular signaling cascade , protein kinase cascade , small GTPase mediated signal transduction , Ras protein signal transduction , positive regulation of cell proliferation , insulin receptor signaling pathway , response to endogenous stimulus , response to hormone stimulus , positive regulation of biosynthetic process , response to organic substance ,regulation of receptor activity , positive regulation of macromolecule biosynthetic process , positive regulation of macromolecule metabolic process , phosphorylation , regulation of phosphate metabolic process , positive regulation of cellular biosynthetic process , response to insulin stimulus , cellular response to insulin stimulus , cellular response to hormone stimulus , positive regulation of kinase activity , regulation of growth , regulation of epidermal growth factor receptor signaling pathway , regulation of cell proliferation , regulation of phosphorylation , positive regulation of catalytic activity , regulation of MAP kinase activity , positive regulation of MAP kinase activity , response to peptide hormone stimulus , regulation of kinase activity , positive regulation of molecular function , positive regulation of DNA replication , regulation of protein kinase activity , positive regulation of protein kinase activity , positive regulation of nucleobase , nucleoside , nucleotide and nucleic acid metabolic process , regulation of DNA metabolic process , positive regulation of DNA metabolic process , positive regulation of nitrogen compound metabolic process , regulation of phosphorus metabolic process , regulation of transferase activity , positive regulation of transferase activity ,

Cytoplasm.; [Isoform p46Shc]: Mitochondrion matrix . Localized to the mitochondria matrix. Targeting of isoform p46Shc to mitochondria is mediated by its first 32 amino acids , which behave as a bona fide mitochondrial targeting sequence. Isoform p52Shc and isoform p66Shc , that contain the same sequence but more internally located , display a different subcellular localization.; [Isoform p66Shc]: Mitochondrion . In case of oxidative conditions , phosphorylation at 'Ser-36' of isoform p66Shc , leads to mitochondrial accumulation. .